EP1888502B1 - Catalytic scriabine reaction - Google Patents
Catalytic scriabine reaction Download PDFInfo
- Publication number
- EP1888502B1 EP1888502B1 EP06744885.2A EP06744885A EP1888502B1 EP 1888502 B1 EP1888502 B1 EP 1888502B1 EP 06744885 A EP06744885 A EP 06744885A EP 1888502 B1 EP1888502 B1 EP 1888502B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- formula
- group
- compound
- optionally substituted
- diacetate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
- C07C67/293—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/91—Dibenzofurans; Hydrogenated dibenzofurans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/54—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Definitions
- the present invention relates to the field of organic synthesis. More particularly it provides a process for making aromatic non-conjugated enol esters or enol ethers from an aromatic compound or moiety and a protected enal compound or moiety, such as an acetal or an acylal. The reaction is promoted by the use of some metal derivatives.
- the Scriabine reaction consists of the reaction between an aromatic compound and an enal or the corresponding acylal (see I. Scriabine in Bull. Soc. Chem.Fr., 1961, 1194 ). This reaction provides an access to the formation of dihydrocinnamic aldehyde derivatives. To the best of our knowledge, all the methods and examples reported in the literature concerning this reaction are at least steochiometric and/or very strong acids (Al salt or in TiCl 4 ), see JP61161241 . For instance one may cite Aguillar et al. in Synthetic Comm. 2004, 2719 . The only exception concerns EP 1574509 , but in said document the are used as substrate only highly electron rich substrates.
- the present invention provides a process for making a compound of the formula wherein the wavy line indicates that the double bond can be in a configuration E or Z or a mixture thereof; each R 1 , when taken separately, one represents a hydrogen atom and the other a C 1 -C 4 alkyl group; or the two R 1 , when taken together, represent a C 3 -C 5 alkanediyl or alkenediyl group optionally substituted; R 2 or R 3 represents, taken separately, a hydrogen atom or a C 1 -C 6 alkyl group; R 2 and R 3 , taken together, may represent a C 3 -C 10 alkanediyl or alkenediyl group optionally substituted; R 4 represents a C 1 -C 7 alkyl or fluorinated alkyl group, a C 7 -C 10 alkylaromatic optionally substituted, a C 1 -C 7 acyl group, or a -COCO
- R 1 to R 6 Possible substituents of R 1 to R 6 are one, two or three halogen atoms or OR a , NR a 2 or R a groups, in which R a is a hydrogen atom or a C 1 to C 10 cyclic, linear or branched alkyl or alkenyl group, preferably a C 1 to C 4 linear or branched alkyl or alkenyl group.
- Possible substituents of Y are one to five groups such as halide atoms or methyl or CF 3 groups.
- the compound of formula (I), or (I') can be in the form of a mixture of isomers.
- the compound of formula (II) is methyl-benzene, then the compound (I) obtained can be in the form of a mixture of the ortho, or meta, and para isomers.
- the invention provides a process for making a compound of formula (I) or (I') wherein R 4 represents a C 1 -C 7 alkyl group, a benzyl group optionally substituted or a C 1 -C 7 acyl group.
- R 2 or R 3 may represent, taken separately, a hydrogen atom or a C 1 -C 4 alkyl group; R 2 and R 3 , taken together, may represent a C 3 , C 4 or C 10 alkanediyl or alkenediyl group optionally substituted.
- R 5 may also represent a C 2 -C 3 alkanediyl or alkenediyl group optionally substituted.
- the starting material are the corresponding compounds of formula (II) and (III), or the corresponding compound of formula (IV).
- the invention provides a process for making a compound of formula (I) by the reaction of a compound of formula (II) with a compound of formula (III).
- compound of formula (II) one may cite the following: benzene optionally substituted by one or two C 1 -C 4 alkyl groups, 1,3-benzodioxole or indane optionally substituted by one or two C 1 -C 4 alkyl groups, and in particular 1,1-dimethyl indane.
- compound of formula (III) one may cite the following: acrolein diethyl acetal, acrolein diacetate, methacrolein diacetate, crotonaldehyde diacetate, tiglyl diacetate, cyclohexenyl carbaldehyde diacetate.
- the invention process is carried out in the presence of one catalyst which is a salt of formula MX n or a compound of formula BY 3 and adducts thereof.
- Said catalyst can be in the anhydrous form or also in the hydrate form, except for those acids which are unstable in the presence of water.
- the anhydrous form is preferred.
- the catalyst is selected from the group consisting of BY 3 and adducts thereof.
- the catalyst is selected from the group consisting of BY 3 and its adducts above mentioned.
- BY 3 can be used alone or in the form of one of its adducts with an ether or a carboxylic acid.
- Specific examples are the adducts of BF 3 with Et 2 O, Bu 2 O or AcOH.
- X is a mono-anion selected from the group consisting of acetylacetonate optionally substituted, Cl - , Br - , C 1-9 carboxylate, a C 1-10 sulphonate, ClO 4 - , BF 4 - , PF 6 - , SbCl 6 - , AsCl 6 - , SbF 6 - , AsF 6 - , BR 7 4 - , wherein R 7 is a phenyl group optionally substituted by one to five groups such as halide atoms or methyl or CF 3 groups, or a R 8 SO 3 - , wherein R 8 is a chlorine or fluoride atom.
- X can be selected from the group consisting of Cl - , Br - and trifluoromethylsulfonate.
- Y is F or C 6 H 5 .
- the catalyst is BF 3 and its adducts with AcOH.
- the catalyst can be added to the reaction medium in a large range of concentrations.
- concentrations ranging from 0.001 to 0.30 molar equivalents, relative to the molar amount of the starting compound (II) or (IV).
- the catalyst concentrations will be comprised between 0.005 and 0.15 molar equivalents. It goes without saying that the optimum concentration of catalyst will depend on the nature of the catalyst and on the desired reaction time.
- catalyst concentrations ranging from 0.1 to 0.30 molar equivalents, relative to the molar amount of the starting compound (III).
- the catalyst concentrations will be comprised between 0.01 and 0.10 molar equivalents. It goes without saying that the optimum concentration of catalyst will depend on the nature of the catalyst and on the desired reaction time.
- catalytic amount we mean here any amount which allow the formation of the desired compound with a molar yield which exceeds the molar equivalents of catalyst added to the reaction mixture.
- the temperature at which the invention's process can be carried out is typically between 0°C and 180°C, more preferably in the range of between 15°C and 100°C.
- a person skilled in the art is also able to select the preferred temperature as a function of the melting and boiling point of the starting and final products.
- a person skilled in the art is also able to select the preferred temperature as a function of the melting and boiling point of the starting and final products as well as of the solvent.
- the process of the invention can be carried out in the presence or in the absence of solvent.
- the presence of a solvent is mandatory only in the case in which the starting compound is a solid compound under the reaction conditions.
- the process is advantageously carried out in the presence of a solvent.
- a solvent is anhydrous or does not contain more than 1 % w/w water.
- Non-limiting examples of such a solvent are C 4 -C 8 ethers, C 3 -C 6 esters, C 3 -C 6 amides, C 6 -C 9 aromatic solvents, C 5 -C 7 linear or branched or cyclic hydrocarbons, C 1 -C 2 chlorinated solvents and mixtures thereof.
- reaction can also be carried out in the presence of a solvent belonging to the family of carboxylic anhydride of formula R 9 C(O)O(O)CR 9 , R 9 representing a C 1 -C 7 alkyl group, a C 7 -C 10 alkylaromatic optionally substituted, a C 1 -C 7 acyl group, optionally containing the corresponding carboxylic acid R 9 COOH.
- R 9 belonging to the family of carboxylic anhydride of formula R 9 C(O)O(O)CR 9
- R 9 representing a C 1 -C 7 alkyl group, a C 7 -C 10 alkylaromatic optionally substituted, a C 1 -C 7 acyl group, optionally containing the corresponding carboxylic acid R 9 COOH.
- R 9 belonging to the family of carboxylic anhydride of formula R 9 C(O)O(O)CR 9
- R 9 representing a C 1 -C 7 alkyl group, a C 7 -C 10 alky
- the compound of formula (III) or (IV) can be made and isolated according to any prior art method.
- compound (III) or (IV) can be also generated in situ, i.e. in the reaction medium just before its use, according to any know prior art method.
- the compound of formula (III) or (IV) is made or generated by a method using the corresponding enal as starting material.
- Another object of the present invention is an invention's process, as defined above, further comprising the step of generating in situ the compound of formula (III) or (IV) starting from the corresponding enal of formula (V) or (V') respectively wherein R 1 , R 2 , R 3 and R 5 have the same meaning indicated above.
- a process comprising the in situ generation of the compound of formula (III) or (I') is particularly useful when said compound (III) or (I') is an acetal or an acylal, the latter being a geminal dicarboxylate.
- another object of the present invention is a process for making a compound of formula (I) or (I'), as defined above, comprising the step of reacting, in the presence of a catalyst as defined above, an enal of formula (V) or (V'), as defined above, with a carboxylic anhydride of formula R 9 C(O)O(O)CR 9 , wherein R 9 has the meaning indicated above.
- aqueous phase was re-extracted with ethyl acetate (150 ml).
- the combined organic phases were washed with saturated aqueous NaHCO 3 solution (100 ml), brine (100 ml), dried over MgSO 4 and the solvents removed in vacuo. Further purification by KugelRohr distillation at 150°C (2.9 x 10 -1 mbar) gave the desired enol acetate as a mixture of isomers (7.2 g, 30%).
- Zinc bromide 50 mg, 0.2 mmol was suspended in a solution of acrolein diacetate (1.6 g, 10 mmol), 2,2 dimethyl dihydrobenzofuran (1.5 g, 10 mmol), in dichloromethane (5 g) and the stirred at ambient temperature for 24 hours. The reaction medium was then diluted with ethyl acetate (25 ml) and the saturated aqueous NaHCO 3 solution (20 ml) was added slowly dropwise. The aqueous phase was re-extracted with ethyl acetate (25 ml).
- BF 3 acetic acid complex (0.2 g, 1 mmol) was added to a stirred solution of 2-methyl indane (13.2 g, 100 mmol) and methacrolein diacetate (8.7 g, 50 mmol) heated at 60°C. The mixture was stirred at 60°C for one hour, then cooled and diluted with ethyl acetate (50 ml), and saturated aqueous NaHCO 3 solution (50 ml) was added slowly dropwise. The aqueous phase was re-extracted with ethyl acetate (50 ml), the combined organic phase was washed with NaHCO 3 (100 ml), dried over MgSO 4 , filtered and the solvents removed in vacuo.
- the aqueous phase was re-extracted with ethyl acetate (50 ml), the combined organic phase was washed with bicarbonate (50 ml) then brine (50 ml), dried over magnesium sulfate, filtered and the solvents removed in vacuo.
- the crude product was purified by Kugelrohr distillation, firstly under moderate vacuum (5-10 mbar) to recover the indane, then under high vacuum (1.0-4.0 x 10 -1 mbar).
- Zinc chloride (0.14 g, 1 mmol, 10 mol%) was added to a stirred solution of 1,3 methylenedioxy benzene (2.4 g, 20 mmol) and methacrolein diacetate (1.72 g, 10 mmol) at ambient temperature. The solution was stirred at ambient temperature for a further 48 hours. The solution was diluted with ethyl acetate (59 ml), and sodium bicarbonate 5% (50 ml), the aqueous phase was re-extracted with ethyl acetate (50 ml), the organic phase was washed with brine (50 ml), dried over magnesium sulfate, filtered and the solvents removed in vacuo.
- Zinc chloride (0.14 g, 1 mmol), was added to a solution of anisole (2.16 g, 20 mmol) and tiglic diacetate (1.86 g, 10 mmol), and the mixture stirred at ambient temperature for 3 hours.
- the solution was diluted with ethyl acetate (25 ml) and saturated sodium bicarbonate (50 ml), the aqueous phase was re-extracted with ethyl acetate (25 ml) the combined organic phases were washed with brine, dried over magnesium sulfate, filtered and the solvents removed in vacuo.
- Acetic anhydride (5 g, 49 mmol) was added to a suspension of FeCl 3 .6H 2 O (1.08 g, 4 mmol) and 2-methyl indane (26.4 g, 200 mmol), after 5 mins crotonaldehyde diacetate (6.88 g, 40 mmol) was added slowly drop wise. The mixture was stirred for a further 7 hours, then poured into brine (50 ml), extracted with ether (100 ml), washed the organic extract with sodium bicarbonate (100 ml), then brine (50 ml), dried over magnesium sulfate, filtered and the solvents removed in vacuo.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Furan Compounds (AREA)
- Saccharide Compounds (AREA)
Description
- The present invention relates to the field of organic synthesis. More particularly it provides a process for making aromatic non-conjugated enol esters or enol ethers from an aromatic compound or moiety and a protected enal compound or moiety, such as an acetal or an acylal. The reaction is promoted by the use of some metal derivatives.
- The Scriabine reaction consists of the reaction between an aromatic compound and an enal or the corresponding acylal (see I. Scriabine in Bull. Soc. Chem.Fr., 1961, 1194). This reaction provides an access to the formation of dihydrocinnamic aldehyde derivatives. To the best of our knowledge, all the methods and examples reported in the literature concerning this reaction are at least steochiometric and/or very strong acids (Al salt or in TiCl4), see
JP61161241 EP 1574509 , but in said document the are used as substrate only highly electron rich substrates. - It is therefore highly desirable to access such dihydrocinnamic aldehyde derivatives by using a catalyzed reaction, and, if possible, catalysts which are more environmentally friendly.
- In order to solve the aforementioned problems, the present invention provides a process for making a compound of the formula
each R1 , when taken separately, one represents a hydrogen atom and the other a C1-C4 alkyl group; or the two R1 , when taken together, represent a C3-C5 alkanediyl or alkenediyl group optionally substituted;
R2 or R3 represents, taken separately, a hydrogen atom or a C1-C6 alkyl group; R2 and R3, taken together, may represent a C3-C10 alkanediyl or alkenediyl group optionally substituted;
R4 represents a C1-C7 alkyl or fluorinated alkyl group, a C7-C10 alkylaromatic optionally substituted, a C1-C7 acyl group, or a -COCOOH or -COCH2COOH group; and R5 represents a C2-C9 alkanediyl or alkenediyl group optionally substituted; comprising the coupling of a compound of formula (II) with a compound of formula (III)
or, respectively, the cyclisation of a compound of formula - a salt of formula MXn, M representing a transition metal selected from the group consisting of Fe, Co, Ni, Cu and Zn, X representing a mono-anion and n is an integer from 1 to 3; and
- a boron compound of formula BY3, wherein Y represents a fluoride or a phenyl group optionally substituted, and anyone of its adducts with a C2-C10 ether or a C1-C8 carboxylic acid.
- Possible substituents of R1 to R6 are one, two or three halogen atoms or ORa, NRa 2 or Ra groups, in which Ra is a hydrogen atom or a C1 to C10 cyclic, linear or branched alkyl or alkenyl group, preferably a C1 to C4 linear or branched alkyl or alkenyl group.
- Possible substituents of Y are one to five groups such as halide atoms or methyl or CF3 groups.
- It is also understood that, when R1 are not hydrogen atoms, the compound of formula (I), or (I'), can be in the form of a mixture of isomers. For example, if the compound of formula (II) is methyl-benzene, then the compound (I) obtained can be in the form of a mixture of the ortho, or meta, and para isomers.
- According to a first embodiment of the invention, the invention provides a process for making a compound of formula (I) or (I') wherein R4 represents a C1-C7 alkyl group, a benzyl group optionally substituted or a C1-C7 acyl group.
- According to a further embodiment, R2 or R3 may represent, taken separately, a hydrogen atom or a C1-C4 alkyl group; R2 and R3, taken together, may represent a C3, C4 or C10 alkanediyl or alkenediyl group optionally substituted.
- Furthermore, R5 may also represent a C2-C3 alkanediyl or alkenediyl group optionally substituted.
- It is understood that in such embodiment the starting material are the corresponding compounds of formula (II) and (III), or the corresponding compound of formula (IV).
- According to a further embodiment of the present invention the invention provides a process for making a compound of formula (I) by the reaction of a compound of formula (II) with a compound of formula (III).
- As non limiting examples of compound of formula (II) one may cite the following: benzene optionally substituted by one or two C1-C4 alkyl groups, 1,3-benzodioxole or indane optionally substituted by one or two C1-C4 alkyl groups, and in particular 1,1-dimethyl indane.
- As non limiting examples of compound of formula (III) one may cite the following: acrolein diethyl acetal, acrolein diacetate, methacrolein diacetate, crotonaldehyde diacetate, tiglyl diacetate, cyclohexenyl carbaldehyde diacetate.
- As mentioned above the invention process is carried out in the presence of one catalyst which is a salt of formula MXn or a compound of formula BY3 and adducts thereof. Said catalyst can be in the anhydrous form or also in the hydrate form, except for those acids which are unstable in the presence of water. However the anhydrous form is preferred.
- Furthermore, according to a particular embodiment of the invention the use of one compound of formula MXn as catalysts is also preferred.
- According to a particular embodiment of the invention, the catalyst is selected from the group consisting of BY3 and adducts thereof.
- According to a particular embodiment of the invention, the catalyst is selected from the group consisting of BY3 and its adducts above mentioned.
- As mentioned above BY3 can be used alone or in the form of one of its adducts with an ether or a carboxylic acid. Specific examples are the adducts of BF3 with Et2O, Bu2O or AcOH.
- According to another embodiment of the invention, X is a mono-anion selected from the group consisting of acetylacetonate optionally substituted, Cl-, Br-, C1-9 carboxylate, a C1-10 sulphonate, ClO4 -, BF4 -, PF6 - , SbCl6 -, AsCl6 -, SbF6 -, AsF6 -, BR7 4 -, wherein R7 is a phenyl group optionally substituted by one to five groups such as halide atoms or methyl or CF3 groups, or a R8SO3 -, wherein R8 is a chlorine or fluoride atom. In particular X can be selected from the group consisting of Cl-, Br- and trifluoromethylsulfonate.
- According to another embodiment of the invention, Y is F or C6H5.
- According to a further embodiment of the invention, the catalyst is BF3 and its adducts with AcOH.
- The catalyst can be added to the reaction medium in a large range of concentrations. As non-limiting examples, one can cite catalyst concentrations ranging from 0.001 to 0.30 molar equivalents, relative to the molar amount of the starting compound (II) or (IV). Preferably, the catalyst concentrations will be comprised between 0.005 and 0.15 molar equivalents. It goes without saying that the optimum concentration of catalyst will depend on the nature of the catalyst and on the desired reaction time.
- One can also cite catalyst concentrations ranging from 0.1 to 0.30 molar equivalents, relative to the molar amount of the starting compound (III). Preferably, the catalyst concentrations will be comprised between 0.01 and 0.10 molar equivalents. It goes without saying that the optimum concentration of catalyst will depend on the nature of the catalyst and on the desired reaction time.
- It is useful here to mention that by "catalytic amount" we mean here any amount which allow the formation of the desired compound with a molar yield which exceeds the molar equivalents of catalyst added to the reaction mixture.
- The temperature at which the invention's process can be carried out is typically between 0°C and 180°C, more preferably in the range of between 15°C and 100°C. Of course, a person skilled in the art is also able to select the preferred temperature as a function of the melting and boiling point of the starting and final products. Of course, a person skilled in the art is also able to select the preferred temperature as a function of the melting and boiling point of the starting and final products as well as of the solvent.
- The process of the invention can be carried out in the presence or in the absence of solvent. As a person skilled in the art can anticipate, the presence of a solvent is mandatory only in the case in which the starting compound is a solid compound under the reaction conditions.
- However, according to a preferred embodiment of the invention, and independently of the physical state of the starting compound, the process is advantageously carried out in the presence of a solvent. Preferably, said solvent is anhydrous or does not contain more than 1 % w/w water.
- Non-limiting examples of such a solvent are C4-C8 ethers, C3-C6 esters, C3-C6 amides, C6-C9 aromatic solvents, C5-C7 linear or branched or cyclic hydrocarbons, C1-C2 chlorinated solvents and mixtures thereof.
- Furthermore, the reaction can also be carried out in the presence of a solvent belonging to the family of carboxylic anhydride of formula R9C(O)O(O)CR9, R9 representing a C1-C7 alkyl group, a C7-C10 alkylaromatic optionally substituted, a C1-C7 acyl group, optionally containing the corresponding carboxylic acid R9COOH. The optional substituents being the same as for R6.
- The compound of formula (III) or (IV) can be made and isolated according to any prior art method. Alternatively, compound (III) or (IV) can be also generated in situ, i.e. in the reaction medium just before its use, according to any know prior art method.
- In particular, preferably the compound of formula (III) or (IV) is made or generated by a method using the corresponding enal as starting material.
- Therefore, another object of the present invention is an invention's process, as defined above, further comprising the step of generating in situ the compound of formula (III) or (IV) starting from the corresponding enal of formula (V) or (V') respectively
- A process comprising the in situ generation of the compound of formula (III) or (I') is particularly useful when said compound (III) or (I') is an acetal or an acylal, the latter being a geminal dicarboxylate.
- Now, when the compound of formula (II) is an acylal, we have also noticed that the catalysts that are able to promote the cyclisation of the acylal are also useful to promote the conversion of the enal into the corresponding acylal.
- Therefore, another object of the present invention, and in fact a particular embodiment of the above-mentioned process, is a process for making a compound of formula (I) or (I'), as defined above, comprising the step of reacting, in the presence of a catalyst as defined above, an enal of formula (V) or (V'), as defined above, with a carboxylic anhydride of formula R9C(O)O(O)CR9, wherein R9 has the meaning indicated above.
- The invention will now be described in further detail by way of the following examples, wherein the abbreviations have the usual meaning in the art, the temperatures are indicated in degrees centigrade (°C). The NMR spectral data were recorded in CDCl3 at 400MHz or 100MHz for 1H or 13C, respectively, the chemical displacements δ are indicated in ppm with respect to TMS as standard, and the coupling constants J are expressed in Hz. All the abbreviations have the usual meaning in the art. Each NMR spectra is provided in respect of the mayor isomer obtained, unless differently specified.
- A solution of FeCl3.6H2O in acetic acid (1.0M, 1.0 ml, 1 mmol) was added slowly dropwise to acetic anhydride (20.4 g, 200 mmol) at 5°C. The solution was allowed to warm to room temperature. A solution of acrolein (5.6 g, 100 mmol), in 2-methyl indane (20.0 g, 151 mmol) and dichloromethane (15 g) was added slowly dropwise to the anhydride solution, maintaining the temperature at about 15°C. The mixture was stirred at 20°C for 4 hours then diluted with ethyl acetate (150 ml), and a saturated aqueous NaHCO3 solution (50 ml) was added slowly dropwise. The aqueous phase was re-extracted with ethyl acetate (150 ml). The combined organic phases were washed with saturated aqueous NaHCO3 solution (100 ml), brine (100 ml), dried over MgSO4 and the solvents removed in vacuo. Further purification by KugelRohr distillation at 150°C (2.9 x 10-1 mbar) gave the desired enol acetate as a mixture of isomers (7.2 g, 30%).
1H-NMR: 1.13 (d, J 6.2, 3H), 2.11 (s, 3H), 2.43-2.59 (m, 3H), 2.98-3.06 (m, 2H), 3.29 (d, J 8.2, 2H), 5.53-5.60 (m, 1H), 6.95 (d, J 7.2, 1H), 7.02 (s, 1H), 7.10 (d, J 7.7, 1H), 7.18 (dt, J 13.8,1, 1H).
13C-NMR: 20.7 (q), 20.9 (q), 33.5 (t), 34.65 (d), 40.7 (t), 41.0 (t), 114.2 (d), 124.4 (d), 126.0 (d), 136.0 (d), 137.5 (s), 141.8 (s), 144.2 (s), 168.2 (s). - A suspension of 2-methyl indane (2.6 g, 20 mmol) and acrolein diacetate (1.6 g, 10 mmol) and zinc bromide (0.25 g, 1 mmol) was stirred for 24 hours at ambient temperature. The reaction medium was then diluted with ethyl acetate (50 ml), and a saturated aqueous NaHCO3 solution (50 ml) was added slowly dropwise. The aqueous phase was re-extracted with ethyl acetate (50 ml). The combined organic extracts were washed with saturated aqueous NaHCO3 solution (50 ml), brine (50 ml), dried over MgSO4, filtered and the solvents removed in vacuo. Further purification of the residue by KugelRohr distillation 180°C (8.0 x 10-1 mbar) gave the enol acetate as a mixture of isomers (0.65 g, 30%) identical to that prepared above.
- Zinc bromide (50 mg, 0.2 mmol) was suspended in a solution of acrolein diacetate (1.6 g, 10 mmol), 2,2 dimethyl dihydrobenzofuran (1.5 g, 10 mmol), in dichloromethane (5 g) and the stirred at ambient temperature for 24 hours. The reaction medium was then diluted with ethyl acetate (25 ml) and the saturated aqueous NaHCO3 solution (20 ml) was added slowly dropwise. The aqueous phase was re-extracted with ethyl acetate (25 ml). The combined organic phase was washed with saturated aqueous NaHCO3 solution (25 ml), brine (25 ml), then dried over MgSO4, filtered and the solvents removed in vacuo. Further purification by KugelRohr distillation 160°C (3.3 x 10-1 mbar) gave the desired enol acetate as a mixture of isomers (0.9 g, 37%).
1H-NMR: 1.45 (s, 6H), 2.11 (s, 3H), 2.97 (s, 2H), 3.25 (d, J 7.7, 2H), 5.55 (dt, 12.3, 7.7, 1H), 6.64 (d, 8.2, 1H), 6.91 (d, J 8.2, 1H), 6.96 (s, 1H), 7.16 (d, 12.3, 1H).
13C-NMR: 20.7 (q), 28.3 (q), 33.0 (t), 42.9 (t), 86.6 (s), 109.2 (d), 114.5 (d), 125.1 (d), 127.4 (s), 127.8 (d), 131.2 (s), 136.0 (d), 157.5 (s), 168.2 (s). - BF3 acetic acid complex (0.2 g, 1 mmol) was added to a stirred solution of 2-methyl indane (13.2 g, 100 mmol) and methacrolein diacetate (8.7 g, 50 mmol) heated at 60°C. The mixture was stirred at 60°C for one hour, then cooled and diluted with ethyl acetate (50 ml), and saturated aqueous NaHCO3 solution (50 ml) was added slowly dropwise. The aqueous phase was re-extracted with ethyl acetate (50 ml), the combined organic phase was washed with NaHCO3 (100 ml), dried over MgSO4, filtered and the solvents removed in vacuo. The residue was further purified by KugelRohr distillation 160°C (6.0 x 10-1 mbar) to give the enol acetate as a mixture of isomers (2.3 g, 19%).
1H-NMR: (major isomer only) 1.13 (d, J 6.7, 3H), 1.60 (d, J 1.5, 3H), 2.14 (s, 3H), 2.44-2.59 (m, 3H), 2.97-3.05 (m, 2H), 3.22 (s, 2H), 6.93 (d, J 6.7, 1H), 6.99 (s, 1H), 7.05 (d, J 1.5, 1H), 7.08 (d, J 7.2, 1H).
13C-NMR: 13.6 (q), 20.8 (q), 20.7 (q), 34.7 (d), 40.2 (t), 40.8 (t), 41.1 (t), 121.6 (s), 124.2 (d), 124.8 (d), 126.6 (d), 131.1 (d), 136.8 (s), 141.8 (s), 144.1 (s), 168.3 (s). - A solution of FeCl3.6H2O in acetic acid (1.0M, 2-3 ml, 2-3 mmol, 5-10% mol) was added to a stirred solution of the indane derivative (35 mmol) acetic anhydride (2 g) and acrolein diacetate (6.5 g, 41 mmol) cooled to 0°C. Stirred for a further 60 minutes at ambient temperature, diluted with ethyl acetate (50 ml), and added saturated sodium bicarbonate (25 ml) slowly dropwise. The aqueous phase was re-extracted with ethyl acetate (50 ml), the combined organic phase was washed with bicarbonate (50 ml) then brine (50 ml), dried over magnesium sulfate, filtered and the solvents removed in vacuo. The crude product was purified by Kugelrohr distillation, firstly under moderate vacuum (5-10 mbar) to recover the indane, then under high vacuum (1.0-4.0 x 10-1 mbar).
-
- 1H-NMR: 0.96 (t, J 7.2, 3H), 1.50 (quintet, J 7.2, 2H), 2.10 (s, 3H), 2.34 (septet, J 7.2, 2H), 2.60-2.46 (m, 2H), 2.95-3.05 (m, 2H), 3.28 (d, J 7.7, 2H), 5.51-5.60 (m, 1H), 6.94 (d, J 7.7, 1H), 7.01 (s, 1H), 7.09 (d, J 7.7, 1H) 7.17 (dt, J 12.3, 1.5, 1H)
- 13C-NMR: 12.8 (q), 20.7 (q), 28.7 (t), 33.5 (t), 38.6 (t), 38.9 (t), 42.2 (d), 114.3 (d), 124.4 (d), 126.1 (d), 136.1 (d), 137.6 (s), 141.8 (s), 144.2 (s), 168.2.
-
- 1H-NMR: 0.88-0.95 (m, 3H), 1.36-1.51 (m, 4H), 2.14 (s, 3H), 2.41-2.59 (m, 2H), 2.95-3.05 (m, 2H), 3.28 (d, J 7.7, 2H), 5.56 (dt, J 12.8,7.2, 1H), 6.94 (d, J 7.7, 1H), 7.01 (s, 1H), 7.08-7.19 (m, 2H).
- 13C-NMR: 14.3 (q), 20.7 (q), 21.5 (t), 33.5 (t), 38.1 (t), 38.9 (t), 40.20 (d), 114.3 (d), 124.4 (d), 126.0 (d), 126.1 (d), 136.1 (d), 137.5 (s), 141.8 (s), 143.7 (s), 144.2 (s), 168.2 (s).
- purified by column chromatography over silica (200 ml) with ether:pentane as eluant (1:19 then 1:9) gave the desired enol acetate (1.1 g, 14%).
1H-NMR: 1.13 (s, 6H), 2.11 (s, 3H), 2.65-2.73 (m, 4H), 3.28 (d, J 7.7, 2H), 5.50-5.60 (m, 1H), 6.94 (d, J 7.7, 1H), 6.98 (s, 1H), 7.07 (d, J 7.7, 1 H), 7.18 (dt, J 10.8, 1.5, 1 H).
13C-NMR: 20.8 (q), 28.8 (q), 33.5 (t), 40.2 (s), 47.4 (t), 47.7 (t), 114.3 (d), 124.7 (d), 126.0 (d), 136.1 (d), 137.5 (s), 141.6 (s), 144.0 (s), 168.2 (s). -
- 1H-NMR: 0.94-1.08 (m, 3H), 1.10-1.14 (m, 3H), 1.16-1.20 (m, 1H), 1.25-1.29 (m, 1H), 2.11 (s, 3H), 2.47-2.58 (m, 3H), 2.90-2.99 (m, 2H), 3.12 (septet, J 6.7, 1H), 3.30 (t, J6.2, 2H), 5.55-5.59 (m, 1H), 6.94-7.20 (m, 4H).
- 13C-NMR: 14.7 (q), 15.2 (q), 20.8 (q), 33.6 (t), 38.0 (d), 39.4 (t), 39.8 (t), 42.0 (d), 42.4 (d), 114.2 (d), 123.6 (d), 124.4 (d), 126.1 (d), 126.2 (d), 134.4 (s), 136.1 (d), 141.0 (s), 149.3 (s), 168.2 (s).
- A solution of FeCl3.6H2O (1.0M in acetic acid, 1.0 ml, 1 mmol) was added to stirred solution of 1,2,3,4 tetrahydronaphthalene (21.65 g, 164 mmol), acetic anhydride (1.4 g, 13.6 mmol), acrolein diacetate (5.4 g, 34 mmol). The solution was stirred for a further 3 hours at ambient temperature, then poured into 5% sodium bicarbonate solution (200 ml), then the aqueous phase was extracted with ether (200 ml). The organic phase was washed with brine, dried over sodium sulfate, filtered and the solvents removed in vacuo. The residue was further purified by column chromatography on silica (300 ml) with cylohexane:ethyl acetate 19:1 and gave the enol acetates as a mixture of regio isomers (α and β (major) naphthyl, plus E and Z).
1H NMR (both isomers): 1.70-1.86 (m, 4H), 2.11 (s, 3H), 2.64-2.80 (m, 4H), 3.21-3.29 (m, 2H), 5.55 (dt, J 12,7, 1H), 6.82-7.25 (m, 4H).
13C NMR(both isomers): 20.7 (q), 22.8 (t), 23.2 (t), 23.3 (t), 23.4 (t), 26.2 (t), 29.2 (t), 29.6 (t), 30.3 (t), 30.8 (t), 33.4 (t), 113.9 (d), 114.7 (d), 126.2 (d), 126.3 (d), 126.8 (d), 128.5 (d), 128.8 (d), 130.1 (d), 135.9 (s), 136.0 (s), 136.9 (d), 137.2 (d), 137.6 (s), 138.1 (s), 138.4 (d), 138.6 (d), 168.2 (s). - A solution of FeCl3.6H2O (1M in acetic acid, 0.3 ml) was added slowly drop wise to a stirred solution of 1,1 dimethyl indane (4.1 g, 28 mmol) acrolein diacetate (1.1 g, 7 mmol) and acetic anhydride (0.3 g, 2.8 mmol). After 2 hours stirring at room temperature, the mixture was poured into brine (50 ml) and the aqueous phase extracted with ether (100 ml). The organic phase was washed with sodium bicarbonate (50 ml), then brine (50 ml), dried over magnesium sulfate, filtered and the solvents removed in vacuo. The residue was further purified by Kugelrohr distillation, 120°C at 10 mbar gave recovered 1,1 dimethyl indane (2.2 g) then distillation at 160°C at 0.3 mbar gave the enol acetates as a mixture of isomers, (1.2 g, yield: 70%).
1H NMR: 1.25 (s, 6H), 1.91 (t, J 7, 2H), 2.11 (s, 3H), 2.84 (t, J 7, 2H), 3.32 (d, J 7, 2H), 5.58 (dt, J 12, 7, 1H), 6.95 (s, 1H), 6.96 (d, J 8, 1H), 7.10 (d, J 8, 1H), 7.18 (dt, J 12, 8, 1H).
13 NMR: 20.7 (q), 28.6 (q), 29.6 (q), 33.6 (t), 41.6 (t), 43.9 (t), 114.2 (d), 121.9 (d), 124.4 (d), 126.3 (d), 136.1 (d), 137.8 (s), 140.8 (s), 153.0 (s),168.1 (s) - A solution of FeCl3.6H2O (1M in acetic acid, 2.5 ml, 2.5 mmol) was added slowly drop wise to a stirred solution of tert-butyl benzene (55 g, 410 mmol) acrolein diacetate (13.5 g, 85 mmol) and acetic anhydride (3.5 g, 34.3 mmol). After 3 hours stirring at room temperature, the mixture was poured into brine (50 ml) and the aqueous phase extracted with ether (2 x 100 ml). The organic phase was washed with sodium bicarbonate (50 ml), then brine (50 ml), dried over magnesium sulfate, filtered and the solvents removed in vacuo. The residue was further purified by column chromatography on silica (500 ml) with cyclohexane then 5:95 ethyl acetate:cyclohexane gave recovered tert-butyl benzene then the enol acetates as a mixture of meta and para isomers, (2.7 g, yield: 14%).
1H NMR: (both isomers)1.31 (s, 9H), 2.11 (s, 3H), 3.30 (d, J 8, 2H) 5.58 (dt, J 12, 8, 1H), 7.12-7.21 (m, 4H), 7.32 (d, J 8, 1H).
13 NMR: 20.7 (q), 30.1 (s), 31.4 (q), 33.0 (t), 34.4 (s), 112.6 (d), 113.9 (d), 125.4 (d), 127.9 (d), 128.0 (d), 134.5 (d), 136.2 (d), 136.7 (d), 136.9 (d), 149.0 (s), 149.2 (s), 168.0 (s), 168.2 (s). - A solution of FeCl3.6H2O (1M in acetic acid, 0.5 ml, 0.5 mmol) was added slowly drop wise to a stirred solution of sec-butyl benzene (11 g, 82 mmol) acrolein diacetate (2.7 g, 17 mmol) and acetic anhydride (0.7 g, 6.8 mmol) in dichloromethane (15 ml). After 3 hours stirring at room temperature, the mixture was poured into saturated sodium bicarbonate (50 ml) and the aqueous phase extracted with ether (100 ml). The organic phase was washed with saturated sodium bicarbonate (50 ml), then brine (50 ml), dried over magnesium sulfate, filtered and the solvents removed in vacuo. The residue was further purified by column chromatography on silica (500 ml) with cyclohexane then 5:95 ethyl acetate:cyclohexane gave recovered sec-butyl benzene then the enol acetate as a mixture of isomers, (1.3 g, yield: 33%).
1H NMR: 0.81 (t, J 7, 3H), 1.21 (d, J 7, 3H), 1.57 (q, J 7, 2H), 2.11 (s, 3H), 2.57 (s, J7, 1H), 3.30 (dd, J 8,1,2H), 5.65-5.52 (m, 1H), 7.10-7.25 (m, 5H).
13 NMR: 12.2 (q), 20.7 (q), 21.8 (q), 31.2 (t), 33.19 (t), 41.3 (d), 114.0 (d), 127.2 (d), 128.2 (d), 136.2 (d), 137.0 (s), 168.2 (s). - Zinc chloride (0.14 g, 1 mmol, 10 mol%) was added to a stirred solution of 1,3 methylenedioxy benzene (2.4 g, 20 mmol) and methacrolein diacetate (1.72 g, 10 mmol) at ambient temperature. The solution was stirred at ambient temperature for a further 48 hours. The solution was diluted with ethyl acetate (59 ml), and sodium bicarbonate 5% (50 ml), the aqueous phase was re-extracted with ethyl acetate (50 ml), the organic phase was washed with brine (50 ml), dried over magnesium sulfate, filtered and the solvents removed in vacuo. The residue was further purified by column chromatography over silica (50 ml), with cylohexane then 1:19 then 1:9 ethyl acetate:cylohexane as eluant. The desired product 1.23 g was further purified by Kugelrohr distillation 125°C at 3.5 x 10-2 mbar, to give the enol acetate, (1.0 g, yield: 53%).
1H NMR: 1.58 (d, J 1.5, 3H), 2.14 (s, 3H), 3.17 (s, 2H), 5.91 (s, 2H), 6.63 (dd, J 8, 1.5, 1H), 6.67 (d, J 1.5, 1H), 6.72 (d, J 8, 1H), 7.02 (d, J 1.5, 1H).
13 NMR: 13.4 (q), 20.8 (q), 40.0 t), 100.9 (t), 108.0 (d), 109.0 (d), 121.3 (s), 121.7 (d) 131.2 (d), 132.8 (s), 146.1 (s), 147.7 (s) and 168.3 (s). - Zinc chloride (0.14 g, 1 mmol), was added to a solution of anisole (2.16 g, 20 mmol) and tiglic diacetate (1.86 g, 10 mmol), and the mixture stirred at ambient temperature for 3 hours. The solution was diluted with ethyl acetate (25 ml) and saturated sodium bicarbonate (50 ml), the aqueous phase was re-extracted with ethyl acetate (25 ml) the combined organic phases were washed with brine, dried over magnesium sulfate, filtered and the solvents removed in vacuo. Further purification by column chromatography over silica (50 ml) with cyclohexane, then 1:19, then 1:9 ethyl acetate cyclohexane gave the enol acetate as a mixture of isomers. Further purification by Kugelrohr distillation 125°C at 3.5 x 10-2 mbar gave the enol acetate as a mixture of isomers, (1.2 g, yield: 51%).
1H NMR: 1.37 (d, J 7, 3H), 1.51 (d 1.5, 3H), 2.13 (s, 3H), 3.37 (q, J 7, 1H), 3.77 (s, 3H), 6.83 (d, J 9, 2H), 7.13 (d, J 9, 2H), 7.13 (m, 1H).
13 C NMR: 12.1 (q), 19.3 (q), 20.8 (q), 42.5 (d), 55.2 (q), 113.6 (d), 128.3 (d), 130.6 (d), 136.2 (s), 158.0 (s), 168.3 (s). - Acetic anhydride (5 g, 49 mmol) was added to a suspension of FeCl3.6H2O (1.08 g, 4 mmol) and 2-methyl indane (26.4 g, 200 mmol), after 5 mins crotonaldehyde diacetate (6.88 g, 40 mmol) was added slowly drop wise. The mixture was stirred for a further 7 hours, then poured into brine (50 ml), extracted with ether (100 ml), washed the organic extract with sodium bicarbonate (100 ml), then brine (50 ml), dried over magnesium sulfate, filtered and the solvents removed in vacuo. The residue was further purified by distillation, 65°C at 10 mbar, gave the recovered 2-methyl indane then distillation of the residue 170°C at 0.1 mbar gave the enol acetate as a mixture of isomers, (4.3 g, yield: 44%).
1H NMR (for both major isomers): 1.11-1.17 (m, 3H), 1.34 (d, J 7, 3/2H), 1.36 (d,J 6.6, 3/2H), 2.07 (s, 3/3H), 2.09 (s, 3/3H), 2.15 (s, 3/3H), 2.45-2.58 (m, 3H), 2.96-3.08 (m, 2H), 3.45 (quintet, J 7, 1/2H), 3.96 (m, 1/2H), 5.03 (dd, J 10, 7, 1/2H), 5.61 (dd, J 12.8, 7, 1/2H), 6.94-7.20 (m, 4H).
13C NMR(for both major isomers): 20.7 (q), 20.9 (q), 22.0 (q), 34.5 (d), 34.8 (d), 40.8 (t), 41.1 (t), 119.3 (d), 123.0 (d), 124.4 (d), 124.8 (d), 126.0 (d), 132.6 (d), 135.0 (d), 141.9 (s), 143.5 (s), 144.2 (d), 168.7 (s). - A solution of FeCl3.6H2O (1M in acetic acid, 0.31 ml) was added slowly dropwise to a stirred solution of anisole (5.53 g, 51 mmol) cyclohexane carbaldehyde diacetate (2.3 g, 10.8 mmol) and acetic anhydride (0.46 g, 4.5 mmol). After 4 hours stirring at room temperature, the mixture was poured into brine (50 ml) and the aqueous phase extracted with ether (2 x 100 ml). The organic phase was washed with sodium bicarbonate (50 ml), then brine (50 ml), dried over magnesium sulfate, filtered and the solvents removed in vacuo. The residue was further purified by column chromatography on silica (500 ml) with cyclohexane then 5:95 ethyl acetate:cyclohexane gave the enol acetates as a mixture of isomers, (2.57 g, 91%).
MS: M(+) 260, 200, 172, 169, 121, 108, 43 m/z. - A solution of FeCl3.6H2O (0.112M in acetic anhydride, 1.2 ml, 0.134 mmol) was added slowly dropwise to 6-phenyl-hex-2-enal (1.8 g, 10 mmol) with stirring at 5°C over 15 minutes. The reaction mixture was allowed to warm slowly to ambient temperature and stirred for a further 20 hours. The dark mixture was poured into saturated sodium bicarbonate solution, then extracted with ether (3 x 10 ml). The combined organic phase was dried over sodium sulfate, filtered and the solvents removed in vacuo. The residue was rapidly distilled by Kugelrohr 140-170°C at 5.0 10-2 mbar to afford the enol acetates (2-(1,2,3,4-tetrahydro-1-naphthalenyl)vinyl acetate) as a mixture of E/Z isomers, 1.8 g, 83%.
- E isomer:
- 1H NMR: 1.68-1.70 (m, 1H), 1.71-1.80 (m, 1H), 1.86-2.01 (m, 2H), 2.12 (s, 3H), 2.72-2.84 (m, 2H), 3.41-3.49 (m, 1H), 5.49 (dd, J 13, 9, 1H), 7.05-7.19 (m, 5H).
- 13 NMR: 20.7 (q), 20.9 (t), 29.6 (t), 30.8 (t), 37.8 (d), 119.5 (d), 125.7 (d), 126.2 (d), 129.2 (d), 129.3 (d), 136.1 (d), 136.9 (s), 137.9 (s), 168.2 (s).
- Z isomer:
- 1H NMR: 1.54-1.64 (m, 1H), 1.73-1.83 (m, 1H), 1.89-2.03 (m, 2H), 2.18 (s, 3H), 2.75-2.86 (m, 2H), 3.99-4.06 (m, 1H), 4.98 (dd, J 10, 6, 1H), 7.05-7.14 (m, 4H), 7.16 (d, J 6, 1H).
- 13 NMR: 20.8 (q), 21.5 (t), 29.6 (t), 30.1 (t), 34.9 (d), 118.7 (d), 125.8 (d), 126.0 (d), 128.9 (d), 129.1 (d), 133.9 (d), 136.8 (s), 138.5 (s), 168.2 (s).
- A solution of FeCl3.6H2O (0.112M in acetic anhydride, 1.2 ml, 0.134 mmol) was added slowly dropwise to 4-methyl-6-phenyl-hex-2-enal (2.0 g, 10.1 mmol) with stirring at 5°C over 15 minutes. The reaction mixture was allowed to warm slowly to ambient temperature and stirred for a further 20 hours. The dark mixture was poured into saturated sodium bicarbonate solution, then extracted with ether (3 x 10 ml). The combined organic phase was dried over sodium sulfate, filtered and the solvents removed in vacuo. The residue was rapidly distilled by Kugelrohr 150-180°C at 5.0 10-2 mbar to afford the enol acetates (2-(2-methyl-1,2,3,4-tetrahydro-1-naphthalenyl)vinyl acetate) as a mixture of isomers, 2:2:1:1, 1.9 g, 82%.
1H NMR (major isomers): 0.96 (d, J 3, 3/2H), 0.98 (d, J 2.5, 3/2 H), 1.41-1.80 (m, 2H), 1.89-2.08 (m, 1H), 2.08 (s, 3/2H), 2.19 (s, 3/2H), 2.80-2.85 (m, 2H), 3.34 (dd, J 9.7, 5, 1/2H), 4.02 (dd, J 10, 5, 1/2H), 4.90 (dd, J 10.7, 6.6, 1/2H), 5.49 (dd, J 12.3, 10.2, 1/2H), 7.06-7.31 (m, 5H).
13C NMR(major isomers): 18.3 (q), 18.9 (q), 20.7 (q), 20.8 (q), 26.7 (t), 26.9 (t), 28.7 (t), 28.8 (t), 32.1 (d), 32.4 (d), 116.0 (d), 117.8 (d), 125.9 (d), 126.0 (d), 128.9 (d), 129.7 (d), 136.9 (s), 138.5 (s), 168.1 (d), 168.2 (d) ppm.
Claims (9)
- A process for making a compound of formulawherein the wavy line indicates that the double bond can be in a configuration E or Z or a mixture thereof;R1, when taken separately, one represents a hydrogen atom and the other a C1-C4 alkyl group; or the two R1, when taken together, represent a C3-C5 alkanediyl or alkenediyl group optionally substituted;R2 or R3 represents, taken separately, a hydrogen atom or a C1-C6 alkyl group; R2 and R3, taken together, may represent a C3-C10 alkanediyl or alkenediyl group optionally substituted;R4 represents a C1-C7 alkyl or fluorinated alkyl group, a C7-C10 alkylaromatic optionally substituted, a C1-C7 acyl group, or a -COCOOH or -COCH2COOH group; andR5 represents a C2-C9 alkanediyl or alkenediyl group optionally substituted;comprising the coupling of a compound of formula (II) with a compound of formula (III)wherein R1 to R3 have the meaning indicated in formula (I) and each R6, taken separately, represents a C1-C7 alkyl or fluorinated alkyl group, a C7-C10 alkylaromatic optionally substituted, a C1-C7 acyl group, or the R6, taken together, represent a COCO or COCH2CO group;or, respectively, the cyclisation of a compound of formulawherein R1 and R3 have the meaning indicated in formula (I), R6 have the meaning indicated in formula (III), and R5have the meaning indicated in formula (I');said processes being characterized in that it is carried out in the presence of a catalytic amount of only one catalyst selected from the group consisting of- a salt of formula MXn, M representing a transition metal selected from the group consisting of Fe, Co, Ni, Cu and Zn, X representing a mono-anion and n is an integer from 1 to 3; and- a boron compound of formula BY3, characterized in that Y represents a fluoride or a phenyl group optionally substituted, and anyone of its adducts with a C2-C10 ether or a C1-C8 carboxylic acid.
- A process according to claim 1, characterized in that the compound of formula (II) is a benzene optionally substituted by one or two C1-C4 alkyl groups or an indane optionally substituted by one or two C1-C4 alkyl groups.
- A process according to claim 1, characterized in that the compound of formula (III) is acrolein diethyl acetal, acrolein diacetate, methacrolein diacetate, crotonaldehyde diacetate, tiglyl diacetate, cyclohexenyl carbaldehyde diacetate.
- A process according to claim 1, characterized in that the catalyst is selected from the group consisting of BY3 and adducts thereof, FeX3, CoX2, NiX2, ZnX2, CuX2 and CuX.
- A process according to claim 1, characterized in that the catalyst is selected from the group consisting of BY3 and its adducts, FeX3, and ZnX2.
- A process according to claim 1, characterized in that X is a mono-anion selected from the group consisting of acetylacetonate optionally substituted, Cl-, Br-, C1-9 carboxylate, a C1-10 sulphonate, ClO4 -, BF4 -, PF6 -, SbCl6 -, AsCl6 -, SbF6 -, AsF6 - , BR7 4 - , wherein R7 is a phenyl group optionally substituted by one to five groups such as halide atoms or methyl or CF3 groups, or a R8SO3 -, wherein R8 is a chlorine or fluoride atom.
- A process according to claim 1, characterized in that X is Cl-, Br- or trifluoromethylsulfonate.
- A process according to claim 1, characterized in that the catalyst is BF3 and its adducts with AcOH, FeCl3, ZnBr2 or ZnCl2.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IB2005001310 | 2005-05-11 | ||
PCT/IB2006/051451 WO2006120639A2 (en) | 2005-05-11 | 2006-05-09 | Catalytic scriabine reaction |
Publications (2)
Publication Number | Publication Date |
---|---|
EP1888502A2 EP1888502A2 (en) | 2008-02-20 |
EP1888502B1 true EP1888502B1 (en) | 2016-07-13 |
Family
ID=37114366
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP06744885.2A Active EP1888502B1 (en) | 2005-05-11 | 2006-05-09 | Catalytic scriabine reaction |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP1888502B1 (en) |
JP (1) | JP5376939B2 (en) |
CN (1) | CN101171223B (en) |
ES (1) | ES2595498T3 (en) |
WO (1) | WO2006120639A2 (en) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP5228920B2 (en) * | 2006-11-13 | 2013-07-03 | 宇部興産株式会社 | Process for producing 1-acyloxy-3- (3,4-methylenedioxyphenyl) -1-propene compound |
EP2562173B1 (en) | 2007-02-15 | 2016-02-10 | Ube Industries, Ltd. | Method for production of 2-methyl-3-(3,4-methylenedioxyphenyl)-propanal |
US8039649B2 (en) | 2007-03-07 | 2011-10-18 | Ube Industries, Ltd. | Method of retaining the quality of 2-methyl-3-(3,4-methylenedioxyphenyl)propanal and process for producing the same |
ES2613091T3 (en) * | 2011-06-30 | 2017-05-22 | Firmenich Sa | Beta-santalol preparation procedure |
US9056826B2 (en) * | 2011-06-30 | 2015-06-16 | Firmenich Sa | Process for the preparation of beta-santalol |
US11312873B2 (en) * | 2019-09-04 | 2022-04-26 | Eastman Chemical Company | Aromatic enol ether paint additives |
EP4149913A1 (en) | 2020-07-24 | 2023-03-22 | Firmenich SA | Process for preparing indene acryladehyde derivatives |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3548006A (en) * | 1963-03-15 | 1970-12-15 | Rhone Poulenc Sa | Aldehydes useful in perfumery |
JPS61151152A (en) * | 1984-12-24 | 1986-07-09 | Mitsubishi Rayon Co Ltd | Production of alkenylidene diacetate |
JPS61161241A (en) | 1985-01-08 | 1986-07-21 | Mitsubishi Rayon Co Ltd | Production of aldehyde derivative |
DE69516036T2 (en) * | 1994-05-31 | 2000-12-21 | Firmenich & Cie | Aromatic compounds and their use in perfumery |
US7173148B2 (en) * | 2002-12-18 | 2007-02-06 | Ube Industries, Ltd. | Process for producing 1-acetoxy-3-(substituted phenyl)propene compound |
-
2006
- 2006-05-09 ES ES06744885.2T patent/ES2595498T3/en active Active
- 2006-05-09 JP JP2008510707A patent/JP5376939B2/en active Active
- 2006-05-09 EP EP06744885.2A patent/EP1888502B1/en active Active
- 2006-05-09 CN CN2006800151490A patent/CN101171223B/en active Active
- 2006-05-09 WO PCT/IB2006/051451 patent/WO2006120639A2/en not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
ES2595498T3 (en) | 2016-12-30 |
WO2006120639A3 (en) | 2007-03-08 |
CN101171223B (en) | 2012-07-04 |
JP2008544955A (en) | 2008-12-11 |
EP1888502A2 (en) | 2008-02-20 |
CN101171223A (en) | 2008-04-30 |
JP5376939B2 (en) | 2013-12-25 |
WO2006120639A2 (en) | 2006-11-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1888502B1 (en) | Catalytic scriabine reaction | |
US5107030A (en) | Method of making 2,7-dimethyl-2,4,6-octatrienedial and derivatives thereof | |
JP5758906B2 (en) | Process for producing m-substituted phenylalkanols by isomerization | |
US7250528B2 (en) | Process for producing indenol esters or ethers | |
CA3174197A1 (en) | Catalytic cannabigerol processes and precursors | |
US7524983B2 (en) | Catalytic scriabine reaction | |
JP2019112380A (en) | Method for producing 3,7-dimethyl-7-octenol and method for producing 3,7-dimethyl-7-octenyl carboxylate compound | |
US11370738B2 (en) | Process for the production of 2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2-butenal | |
EP1948584B1 (en) | Process for the preparation of cyclopentanone derivatives | |
EP3464235B1 (en) | Process for the preparation of polysantol-type compounds | |
JP4649945B2 (en) | Method for producing 3-arylglutaric anhydride | |
CN106488900B (en) | Prins reaction on hindered substrates | |
JP5817574B2 (en) | Distillation method of cis-3-hexenal | |
JPS6241587B2 (en) | ||
JP2023504975A (en) | Method for preparing 1-indanone compounds by intramolecular Friedel-Crafts reaction of α,α-dialkylmalonate derivatives | |
JP2022528611A (en) | New enol acetate | |
JP2022528612A (en) | New Enol Acetate (II) | |
JP2005289981A (en) | Method for producing tetralones | |
JPS6254411B2 (en) | ||
JPH0214337B2 (en) | ||
JPS6254294B2 (en) | ||
SE127238C1 (en) |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20071211 |
|
AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR |
|
DAX | Request for extension of the european patent (deleted) | ||
17Q | First examination report despatched |
Effective date: 20090810 |
|
GRAP | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
|
INTG | Intention to grant announced |
Effective date: 20160208 |
|
GRAS | Grant fee paid |
Free format text: ORIGINAL CODE: EPIDOSNIGR3 |
|
GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR |
|
REG | Reference to a national code |
Ref country code: GB Ref legal event code: FG4D |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: REF Ref document number: 812165 Country of ref document: AT Kind code of ref document: T Effective date: 20160715 Ref country code: CH Ref legal event code: EP |
|
REG | Reference to a national code |
Ref country code: IE Ref legal event code: FG4D |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R096 Ref document number: 602006049591 Country of ref document: DE |
|
REG | Reference to a national code |
Ref country code: LT Ref legal event code: MG4D |
|
REG | Reference to a national code |
Ref country code: NL Ref legal event code: MP Effective date: 20160713 |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: MK05 Ref document number: 812165 Country of ref document: AT Kind code of ref document: T Effective date: 20160713 |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FG2A Ref document number: 2595498 Country of ref document: ES Kind code of ref document: T3 Effective date: 20161230 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: FI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: LT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: IT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: NL Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: IS Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20161113 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: GR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20161014 Ref country code: SE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: BE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: LV Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: PT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20161114 Ref country code: PL Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: AT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R097 Ref document number: 602006049591 Country of ref document: DE |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 12 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: EE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: RO Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 |
|
PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: BG Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20161013 Ref country code: SK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: DK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: CZ Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 |
|
26N | No opposition filed |
Effective date: 20170418 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20170531 Ref country code: SI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: MC Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 |
|
REG | Reference to a national code |
Ref country code: IE Ref legal event code: MM4A |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20170509 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20170509 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 13 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: HU Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO Effective date: 20060509 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: CY Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20160713 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: TR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R081 Ref document number: 602006049591 Country of ref document: DE Owner name: FIRMENICH SA, CH Free format text: FORMER OWNER: FIRMENICH SA, GENEVA, CH |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PCOW Free format text: NEW ADDRESS: 7, RUE DE LA BERGERE, 1242 SATIGNY (CH) |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: CH Payment date: 20210415 Year of fee payment: 16 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LI Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20220531 Ref country code: CH Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20220531 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: GB Payment date: 20230330 Year of fee payment: 18 |
|
P01 | Opt-out of the competence of the unified patent court (upc) registered |
Effective date: 20230518 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FR Payment date: 20230421 Year of fee payment: 18 Ref country code: ES Payment date: 20230602 Year of fee payment: 18 Ref country code: DE Payment date: 20230331 Year of fee payment: 18 |